Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial
Abstract Lerociclib (GB491), a highly selective oral CDK4/6 inhibitor, has displayed anti-tumor activity and differentiated safety and tolerability profile in previous ph1/2 clinical trials. The LEONARDA-1, a randomized, double-blind, phase III study, was conducted to evaluate the efficacy and safet...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56096-2 |
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| author | Binghe Xu Qingyuan Zhang Yang Luo Zhongsheng Tong Tao Sun Changping Shan Xinlan Liu Yumin Yao Bing Zhao Shusen Wang Xiaohua Zeng Changlu Hu Xi Yan Xiaojia Wang Hongyan Jia Zhendong Chen Fuming Qiu Xinhong Wu Deyong Zhang Tong Li |
| author_facet | Binghe Xu Qingyuan Zhang Yang Luo Zhongsheng Tong Tao Sun Changping Shan Xinlan Liu Yumin Yao Bing Zhao Shusen Wang Xiaohua Zeng Changlu Hu Xi Yan Xiaojia Wang Hongyan Jia Zhendong Chen Fuming Qiu Xinhong Wu Deyong Zhang Tong Li |
| author_sort | Binghe Xu |
| collection | DOAJ |
| description | Abstract Lerociclib (GB491), a highly selective oral CDK4/6 inhibitor, has displayed anti-tumor activity and differentiated safety and tolerability profile in previous ph1/2 clinical trials. The LEONARDA-1, a randomized, double-blind, phase III study, was conducted to evaluate the efficacy and safety of lerociclib in HR+/HER2− locally advanced or metastatic breast cancer patients, who had relapsed or progressed on prior endocrine therapy. A total of 275 patients were randomized at 1:1 ratio to receive lerociclib (137 patients, 150 mg twice daily) or placebo (138 patients) plus fulvestrant. Progression-free survival (PFS) assessed by investigators was significantly improved in lerociclib arm versus placebo arm (11.07 vs 5.49 months; hazard ratio, 0.451, 95% CI: 0.311-0.656, P = 0.000016), meeting the pre-specified primary endpoint. The secondary endpoints included PFS assessed by Blinded Independent Central Review (BICR), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), safety and tolerability and pharmacokinetic profile. DOR is not reported, and OS data was immature at the data cut-off but unplanned ad hoc analysis is reported. These findings support lerociclib plus fulvestrant as a treatment option for patients with HR+/HER2− endocrine-resistant advanced breast cancer (ABC). (Funded by Genor Biopharma; LEONARDA-1 ClinicalTrials.gov identifier, NCT05054751.) |
| format | Article |
| id | doaj-art-daa78910e2ad47fe86030945083e81b9 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-daa78910e2ad47fe86030945083e81b92025-01-19T12:30:20ZengNature PortfolioNature Communications2041-17232025-01-011611910.1038/s41467-025-56096-2Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trialBinghe Xu0Qingyuan Zhang1Yang Luo2Zhongsheng Tong3Tao Sun4Changping Shan5Xinlan Liu6Yumin Yao7Bing Zhao8Shusen Wang9Xiaohua Zeng10Changlu Hu11Xi Yan12Xiaojia Wang13Hongyan Jia14Zhendong Chen15Fuming Qiu16Xinhong Wu17Deyong Zhang18Tong Li19National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeHarbin Medical University Cancer HospitalNational Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin Medical University Cancer Institute and HospitalCancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and InstituteThe Affiliated Hospital of Jining Medical UniversityGeneral Hospital of Ningxia Medical UniversityLiaocheng People’s HospitalCancer Hospital of Xinjiang Medical UniversitySun Yat-sen University Cancer CenterBreast Cancer Center, Affiliated Cancer Hospital of Chongqing UniversityAnhui Provincial Cancer HospitalWest China Hospital, Sichuan UniversityCancer Hospital of the University of Chinese Academy of Sciences/Zhejiang Cancer Hospital, Institute of Cancer and Basic Medicine, Chinese Academy of SciencesThe First Hospital of Shanxi Medical UniversityThe Second Affiliated Hospital of Anhui Medical UniversityThe Second Affiliated Hospital Zhejiang University School of MedicineHubei Cancer HospitalGenor Biopharma Co., LtdGenor Biopharma Co., LtdAbstract Lerociclib (GB491), a highly selective oral CDK4/6 inhibitor, has displayed anti-tumor activity and differentiated safety and tolerability profile in previous ph1/2 clinical trials. The LEONARDA-1, a randomized, double-blind, phase III study, was conducted to evaluate the efficacy and safety of lerociclib in HR+/HER2− locally advanced or metastatic breast cancer patients, who had relapsed or progressed on prior endocrine therapy. A total of 275 patients were randomized at 1:1 ratio to receive lerociclib (137 patients, 150 mg twice daily) or placebo (138 patients) plus fulvestrant. Progression-free survival (PFS) assessed by investigators was significantly improved in lerociclib arm versus placebo arm (11.07 vs 5.49 months; hazard ratio, 0.451, 95% CI: 0.311-0.656, P = 0.000016), meeting the pre-specified primary endpoint. The secondary endpoints included PFS assessed by Blinded Independent Central Review (BICR), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), safety and tolerability and pharmacokinetic profile. DOR is not reported, and OS data was immature at the data cut-off but unplanned ad hoc analysis is reported. These findings support lerociclib plus fulvestrant as a treatment option for patients with HR+/HER2− endocrine-resistant advanced breast cancer (ABC). (Funded by Genor Biopharma; LEONARDA-1 ClinicalTrials.gov identifier, NCT05054751.)https://doi.org/10.1038/s41467-025-56096-2 |
| spellingShingle | Binghe Xu Qingyuan Zhang Yang Luo Zhongsheng Tong Tao Sun Changping Shan Xinlan Liu Yumin Yao Bing Zhao Shusen Wang Xiaohua Zeng Changlu Hu Xi Yan Xiaojia Wang Hongyan Jia Zhendong Chen Fuming Qiu Xinhong Wu Deyong Zhang Tong Li Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial Nature Communications |
| title | Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial |
| title_full | Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial |
| title_fullStr | Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial |
| title_full_unstemmed | Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial |
| title_short | Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial |
| title_sort | lerociclib plus fulvestrant in patients with hr her2 locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy leonarda 1 a phase iii randomized trial |
| url | https://doi.org/10.1038/s41467-025-56096-2 |
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